This invention relates to new coumaran derivatives which are substituted at the 3-position.
More particularly, this invention relates to compounds of the formula ##STR2## wherein R is a lower alkyl group, R.sup.0 is hydrogen or an acyl group, R.sup.1 and R.sup.2 are lower alkyl groups which may optionally be substituted or wherein R.sup.1 and R.sup.2 are combined to form a butadienylene group which may optionally be substituted, R.sup.3 and R.sup.4 are hydrogen or alkyl groups which may optionally be substituted or wherein R.sup.3 and R.sup.4 are combined to form a polymethylene group; and R.sup.5 is a lower alkyl, aromatic or heterocyclic group which may optionally be substituted, or pharmaceutically acceptable salts thereof.
Hitherto, related coumaran derivatives which are unsubstituted at the 3-position have been prepared and an antioxidant activity thereof are known [see J. Am. Chem. Soc., 105, 5950 (1983), ibid., 107, 7053 (1985)]. However, the above coumaran derivatives which are substituted at the 3-position as well as their phamaceutical activities have not been reported until now.
The present inventors succeeded in synthesizing various new coumaran derivatives which are substituted at the 3-position, and unexpectedly found that these compounds exert excellent pharmaceutical activities, such as cardiovascular system improving action and antiallergic action, e.g. scavenging action of active oxygen species which are produced in excess in living bodies, inhibition of thromboxane A.sub.2 synthetase (thromboxane A.sub.2 exerts coagulation of blood platelet as well as contraction of blood vessels) or inhibition or control of 5-lipoxygenase which is a key enzyme for the biosynthesis of leukotrienes.
Leukotrienes are potent chemical mediators for allergic or inflammatory reactions, and are considered to cause constriction of peripheral airways in the lung, being related to respiration distress accompanied by bronchial asthma. Also, leukotrienes possess the capabilities to enhance the capillary permeability and to strongly produce chemotactic activity of leukocytes and are intimately associated with edema and cellular infiltration, which are typical symptoms of inflammation.